peripheral vision loss examination a 71-year-old woman ... · 12/31/2016 · case 3....

Grand RoundsA 71-year-old woman with decreased vision, nyctalopia, andperipheral vision lossRavi Parikh, MD, MPH,

a Miguel A. Materin, MD,

a,b Robert Lesser, MD,

c Joachim Baehring, MD,

PhD,b,d

Mario Sznol, MD,b,e

and Jennifer A. Galvin, MDa

Author affiliations: aDepartment of Ophthalmology and Visual Science, Yale University, New Haven, Connecticut;bSmilow Hospital at Yale New Haven Hospital;cEye Care Group, New Haven, Connecticut;dDepartment of Neurology, Yale University;eDepartment of Internal Medicine, Yale University

HistoryA 71-year-old woman was referred to the Department ofOphthalmology and Visual Science, Yale University, foran evaluation of decreased vision, worsening nightvision, and peripheral vision loss in the left eye of 3months’ duration. She had a history of right ductalbreast carcinoma in 1993 that was treated with a lum-pectomy and radiation, with no known metastases. Shealso had a stage II-A melanoma of the left arm excisedin 2011, gout, and hypertension. She denied flashes,floaters, or eye pain and had no history of eye surgery oreye trauma. Family history of eye disease was noncon-tributory.

ExaminationOn initial presentation, best-corrected visual acuitymeasured 20/20+ in each eye. Three months later, onpresentation at Yale University, visual acuities were20/25 +2 in the right eye and at 20/30 −1 in the left eye.Anterior segment examination in each eye was unre-markable except for 1+ nuclear sclerotic cataract in theright eye and trace cortical cataract in the left eye. Pupilswere round and equally reactive, and there was no rela-tive afferent pupillary defect. Ishihara plates were 14/14in each eye. Ocular motility was full, and the patient wasorthotropic.

Dilated fundus examination of the right eye showed novitreous cells, a titled, sharp, pink optic nerve, and a flatmacula with a good foveal reflex. In the left eye, therewere 2+ vitreous cells with a tilted optic nerve with tem-

poral pallor and a trace epiretinal membrane in the mac-ula. Both optic nerves had a cup-to-disc ratio of 0.1. Ret-inal vasculature in both eyes showed mild arteriolarattenuation.

Goldmann visual field testing of the right eye showedI-4e reduced to 20° circumferentially and V-4e with mildreduction superiorly to 50° and mild reduction tempo-rally to 70° (Figure 1A); in the left eye, I-3e reduced to10° circumferentially and III-4e and V-4e moderatelyreduced to 35°–40° superiorly and reduced inferiorly to55°–60° (Figure 1B).

Ancillary TestingMagnetic resonance imaging of the brain with and with-out contrast was negative for metastatic disease. No fur-ther genetic tests for neoplasm were recommended bythe oncology team.

Full-field electroretinogram (ff ERG) in each eyeshowed, in photopic (light adaptation) conditions, nor-mal a-wave and decreased b-wave (Figure 2A). The a-wave was −40.13 µV in the right eye and −40.67 µV inthe left eye as well as 14 ms and 17 ms, respectively(normal range, −31.17 ± 20.34 µV and 12.87 ± 2.05 ms).The b-wave was abnormal, at 66.4 µV in the right eyeand 72.48 µV in the left eye and 38 ms (normal range,117.1 ± 43.44 µV and 29.81 ± 3.88 ms). In single-flashscotopic (dark adaptation) conditions, there were broad-ened a-waves and decreased b-waves as well as adecreased b/a ratio. (Figure 2B). The a-wave is −213.6µV in the right eye and −224 µV in the left eye as well

Published December 31, 2016.Copyright ©2016. All rights reserved. Reproduction in whole or in part in any form or medium without expressed written permission of theDigital Journal of Ophthalmology is prohibited.doi:10.5693/djo.02.2016.06.001Correspondence: Ravi Parikh, MD, MPH, 40 Temple Street, 3rd floor, New Haven, CT 06510 (email: [email protected]).

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as 19 ms and 20 ms, respectively (normal range, −154.3± 73.08 µV and 15.5 ± 6.13 ms). The b-wave in contrastwas abnormal. The b-wave measured to 133.7 µV in theright eye and 117.6 µV in the left eye and 105 ms and 97ms, respectively (normal range, 286.6 ± 182.6 µV and48.68 ± 8.52 ms).

Laboratory work-up included an evaluation for paraneo-plastic disease. Serum sent to Athena Diagnostics (Marl-borough, MA) were negative for the antiretinal autoanti-bodies against the 23kDa cancer-associated retinopathy(CAR) recoverin protein; but serum sent to the OcularImmunology Laboratory at Casey Eye Institute (Port-land, Oregon) were positive for the antiretinal autoanti-bodies against the 46kDa enolase protein.

Vitreous biopsy of the left eye showed atypical lympho-cytes, inconclusive for vitreous lymphoma. The flowcytometry result demonstrated a “paucicellular specimenwith scattered atypical lympocytes.”

Fluorescein angiogram showed no hallmark “leopardspot” changes at the level of the retinal pigment epithe-lium. Thus, the overall clinical picture was more sugges-tive of a smoldering low-grade vitritis rather than anocular lymphoma.

Spectral domain optical coherence tomography (SD-OCT) of the maculae did not appear to show attenuationof the ellipsoid zone (Figure 3). Further fundus auto-fluorescence also did not show any ring maculopathy(Figure 4). Fundus photographs confirmed clinicalexamination findings, showing only a mild attenuationof the vessels with no apparent maculopathy in eithereye (Figure 5).

A positron emission tomography computerized tomogra-phy (CT) scan showed hypermetabolic uptake in a 4.8cm left axillary lymph node without any other patho-logic uptake. A left axillary lymph node dissectionrevealed involvement of one lymph node for melanoma,whereas six additional lymph nodes were negative formetastatic disease.

TreatmentAfter the diagnosis of melanoma-associated retinopathywas made, our patient was treated with intravenousimmunoglobulin (2 mg/kg) for 6 months, resulting inher having a stable visual acuity (20/30 ± 2 in each eye).Of note, an improvement in her night vision wasobserved subjectively; however, repeat ffERG findingswere unchanged.

Differential DiagnosisOur differential diagnosis included intraocular lym-phoma, melanoma-associated retinopathy (MAR), CAR,and metastatic disease.

Diagnosis and DiscussionCAR and MAR are both rare paraneoplastic syndromesthat can be distinguished by clinical symptoms, funduscharacteristics, and electrophysiology findings. Small-cell lung cancer has been most frequently reported as theprimary cancer in CAR; breast and endometrial cancershave also been reported but less frequently.1 CAR typi-cally presents with loss of central vision, reduced colorvision, a ring scotoma, photopsias, and decreased a-wave and b-wave on ffERG.2 MAR typically presentswith rapid onset of photopsias, scotomata, decreased

Figure 1. Goldmann visual field: left eye (A), right eye (B).

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night vision, and variable loss of peripheral or paracen-tral vision.3,4

Our patient had positive antiretinal autoantibodiesagainst the 46-kDa enolase protein, which is also associ-ated with CAR; but, positive antiretinal autoantibodiesare also found in 10% of healthy patients and in variousautoimmune diseases.5

Our patient did not have any other paraneoplastic orantiretinal autoantibodies. The ffERG finding helpedconfirm the diagnosis of MAR. The proposed patho-physiology of MAR is due to antibodies which target thedepolarizing bipolar cells.6 In MAR, the photopic ffERGshows a decreased b-wave with a relatively normal a-wave, whereas the scotopic ffERG shows a markedly

Figure 2. A, Photopic full-field electroretinogram (ffERG), right eye and left eye. B, Single-flash scotopic ffERG, right eye and left eye.

Parikh et al. 87





decreased b wave with decreased b/a wave ratio. InCAR, on the other hand, the photopic and scotopicffERG shows a decreased a-wave and decreased b-wave.7

Both of these paraneoplastic syndromes can be treatedwith immunomodulation. Our patient was treated withintravenous immunoglobulin.8 Although no largerandomized trials exist, visual improvement in CAR has

been reported in the majority of patients receiving corti-costeroid treatment, although it has been noted that somepatients with autoimmune retinopathies have improvedwith a combination of plasmapheresis and corticosteroidtherapy.1

Visual loss in patients with a cancer history may be dueparaneoplastic syndromes, treatment toxicity and ocularmetastases. In addition to clinical evaluation, serologies

Figure 3. Optical coherence tomography of the macula: right eye (A) and left eye (B), with arrow indicating the inner segment–outer seg-ment / ellipsoid zone or ellipsoid portion of inner segment (IS-OS/EZ or EPIS).

Figure 4. Fundus autofluorescence: right eye (A) and left eye (B).

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and electrophysiology testing are important to establisha diagnosis. A diagnosis of a paraneoplastic diseaseshould prompt evaluation of a patient for a primary can-cer, metastatic disease, or progressing systemic cancer.

References1. Hooks JJ, Tso MS, Detrick B. Retinopathies associated with antireti-

nal antibodies. Clin Diagn Lab Immunol 2001;8:853-8.2. Goldstein SM, Syed NA, Milam AH, Maguire AM, Lawton TJ,

Nichols CW. Cancer-associated retinopathy. Arch Ophthalmology1999;117:1641-5.

3. Lu Y, Jia L, He S, et al. Melanoma-associated retinopathy: a para-neoplastic autoimmune complication. Arch Ophthalmology2009;127:1572-80.

4. Myers DA, Bird BR, Ryan SM, et al. Unusual aspects of melanoma.Case 3. Melanoma-associated retinopathy presenting with nightblindness. J Clinical Oncology 2004;22:746-8.

5. Grewal D, Fishman GA, Jampol LM. Autoimmune retinopathy andantiretinal antibodies: a review. Retina 2014;34:827-45.

6. Borkowski LM, Grover S, Fishman GA, Jampol LM. Retinal find-ings in melanoma-associated retinopathy. Am J Ophthalmol2001;132:273-5.

7. Lei B, Bush RA, Milam AH, Sieving PA. Human Melanoma Asso-ciated Retinopathy (MAR) antibodies alter retinal-on response ofthe monkey ERG in vivo. Invest Ophthalmol Vis Sci 2000;41:262-6.

8. Guy J, Aptsiauri N. Treatment of paraneoplastic visual loss withintravenous immunoglobulin. Arch Ophthalmol 1999;127:612-4.

Figure 5. Fundus photographs of the right eye (A) and left eye (B).

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peripheral vision loss examination a 71-year-old woman ... · 12/31/2016 · case 3....

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